Comparison of reporting rates of arthritis and arthralgia following AstraZeneca, Pfizer-BioNTech, Moderna, and Janssen vaccine administration against SARS-CoV-2 in 2021: analysis of European pharmacovigilance large-scale data.

This study aimed to investigate the reporting rates of arthritis and arthralgia following the administration of four vaccines against SARS-CoV-2: Pfizer-BioNTech (Tozinameran), Moderna (CX-024414), AstraZeneca (Chadox1 NCOV-19), and Janssen (AD26.COV2.S) in 2021. We used data from the EudraVigilance database, specifically analyzing spontaneous reports of suspected adverse reactions (ADRs) from the European Union (EU)/European Economic Area (EEA) region. Age-group-specific reporting rates were calculated by dividing the number of arthralgia and arthritis reports per 1,000,000 vaccine doses administered per age group. Reporting rates were compared using a rate ratio among the four vaccines, using the AstraZeneca vaccine as a comparator. The AstraZeneca vaccine was associated with the highest rate of arthralgia across all age groups. Arthritis reporting rates were significantly lower, with the AstraZeneca vaccine having the highest rates in most age groups, except the 60-69 and 80+ groups, where the Janssen and Pfizer-BioNTech vaccines demonstrated higher reporting rates, respectively. The distribution of arthritis rates did not follow the arthralgia pattern, being higher in the 50-79 age group. This study is the first spontaneous reporting system analysis of arthritis reporting rates post-SARS-CoV-2 vaccination at a European level, revealing a higher reporting of suspected musculoskeletal adverse reactions after AstraZeneca vaccination. The findings underscore the need to consider commonly reported events like arthralgia in risk-benefit assessments prior to vaccination against SARS-CoV-2. Given the high prevalence of rheumatic and musculoskeletal diseases and vaccine hesitancy in this population, our results could influence vaccine choice and acceptance.

Angiotensin-converting enzyme 1 gene polymorphisms in patients with systemic sclerosis-associated interstitial lung disease: a single centre retrospective observational study.

Angiotensin-converting enzyme (ACE) 1 gene polymorphisms have been associated with vascular permeability, alveolar endothelial dysfunction and fibroblast proliferation and have been studied in pulmonary diseases such as COPD and idiopathic pulmonary fibrosis. Similar mechanisms of ACE 1 polymorphisms have been seen in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD). We are presenting a retrospective observational study in patients with SSc-ILD and analysing the association of ACE 1 gene polymorphisms (DD, II and ID) with the features of SSc, changes in pulmonary function tests (PFTs) and lung HRCT over three different periods of time (at the time of the diagnosis, 5 and 10 years after the diagnosis). The aim of the study was to determine whether ACE 1 gene polymorphisms have an effect on the severity of SSc-ILD. We found no statistically significant differences in the development and severity of SSc-ILD and changes in PFTs between subgroups of ACE 1 gene polymorphism over the analysed periods (at the time of diagnosis HRCT changes p = 0.270, FEV1 p = 0.483, FVC p = 0.497, DLco p = 0.807, after 5 years HRCT changes p = 0.163, FEV1 p = 0.551, FVC p = 0.362, DLco p = 0.620 and 10 years of follow-up HRCT changes p = 0.853, FEV1 p = 0.589, FVC p = 0.328, DLco p = 0.992). However, patients with the ID genotype showed a significant reduction in FEV1 after 10 years of follow-up in comparison to baseline levels (91.0 (IR 80.0-105.0) at the time of diagnosis and 84.0 (IR 69.0-99.0) after 10 years, p = 0.014). Our study suggests that ACE 1 gene polymorphisms do not have a role in the severity of SSc-ILD. Further studies are needed to explain the exact role of ACE 1 gene polymorphisms in SSc-ILD and SSc in general.

Real world experience with nintedanib in connective tissue disease-related interstitial lung disease: a retrospective cohort study.

Various connective tissue diseases tend to affect specific organs, lungs being the organ with the most serious repercussions and consequences. The diagnosis of interstitial lung disease makes the treatment more difficult and worsens long-term prognosis and overall survival. Positive results from the registration studies of nintedanib led to approval of the drug for the treatment of idiopathic pulmonary fibrosis and chronic fibrosing interstitial lung diseases in connective tissue diseases. After registration, real-world data on the use of nintedanib are being collected in everyday clinical practise. The objective of the study was to collect and analyse real world experience gathered after the registration of nintedanib for the treatment of CTD-ILD and to show if the positive results collected from a homogeneous and "representative" study population can be applied to everyday clinical practice. We are presenting a retrospective observational case-series study of patients treated with nintedanib from the three largest Croatian centers specialised in the treatment of connective tissue diseases with interstitial lung diseases. Stabilisation or improved of lung function tests was reported in 68% of patients when changes in predicted FVC were observed and in 72% of patients when changes in DLco were analysed. Almost all of the reported patients (98%) were treated with nintedanib as an add-on drug to immunosuppressants. The most common side-effects were gastrointestinal symptoms and abnormal liver function tests in less extent. Our real-world data confirm the tolerability, efficacy and similar side-effects of nintedanib as reported in pivotal trials. Key Points • Interstitial lung disease is a common manifestation of several connective tissue diseases and its progressive fibrosing phenotype contributes to high mortality rate and many unmet needs regarding the treatment remain. • Registration studies of nintedanib obtained sufficient data and positive results to support approval of the drug. • Real-world evidence from our CTD-ILD centres confirm the clinical trial data regarding efficacy, tolerability and safety of nintedanib.

The risk of developing non-Hodgkin lymphoma and the mortality rate in primary Sjögren's syndrome: a single-centre, retrospective cohort study.

Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is manifested by the sensation of dry eyes and dry mouth. The higher incidence of non-Hodgkin lymphoma (NHL) among pSS has already been extensively researched. However, there are uncertanties whether the mortality risk in pSS patients and in pSS patients with NHL is increased. The purpose of this study was to describe the prevalence of NHL among pSS patients and to calculate their mortality risk. We retrospectively analysed data on 1367 patients treated in our rheumatology department under the ICD-10 code M35.0. The study finally recruited 155 patients who met the 2016 ACR/EULAR criteria for the diagnosis of pSS. Descriptive statistics was used in data analysis. We applied the indirect standardization by age to compare the incidence rate of NHL in our cohort to general population. Additionally, we compared the mortality in our study to the general population by calculating the standardized mortality ratio (SMR). The overall incidence rate of NHL was 440 per 100,000 patient-years. The SIR compared to the general population was 30.13 (95% CI 12.87-54.63). The overall mortality rate of pSS patients in our cohort was nearly identical to that of the general population (SMR = 0.98 [95% CI (0.47-1.69)]). This study confirms that there are significant differences in lymphoma prevalence, histology, and prognosis across the studied populations. Furthermore, this study found that patients with pSS have similar mortality risk as the general population, and no patient in our cohort died from NHL.

Cutaneous Manifestations, Clinical Characteristics, and Prognosis of Patients With Systemic Sclerosis Sine Scleroderma: Data From the International EUSTAR Database.

Importance: Systemic sclerosis (SSc) sine scleroderma (ssSSc) is a subset of SSc defined by the absence of skin fibrosis. Little is known about the natural history and skin manifestations among patients with ssSSc. Objective: To characterize the clinical phenotype of patients with ssSSc compared with patients with limited cutaneous SSc (lcSSc) and diffuse cutaneous SSc (dcSSc) within the EUSTAR database. Design, Setting, and Participants: This longitudinal observational cohort study based on the international EUSTAR database included all patients fulfilling the classification criteria for SSc assessed by the modified Rodnan Skin score (mRSS) at inclusion and with at least 1 follow-up visit; ssSSc was defined by the absence of skin fibrosis (mRSS = 0 and no sclerodactyly) at all available visits. Data extraction was performed in November 2020, and data analysis was performed from April 2021 to April 2023. Main Outcomes and Measures: Main outcomes were survival and skin manifestations (onset of skin fibrosis, digital ulcers, telangiectasias, puffy fingers). Results: Among the 4263 patients fulfilling the inclusion criteria, 376 (8.8%) were classified as having ssSSc (mean [SD] age, 55.3 [13.9] years; 345 [91.8%] were female). At last available visit, in comparison with 708 patients with lcSSc and 708 patients with dcSSc with the same disease duration, patients with ssSSc had a lower prevalence of previous or current digital ulcers (28.2% vs 53.1% in lcSSc; P < .001; and 68.3% in dcSSc; P < .001) and puffy fingers (63.8% vs 82.4% in lcSSc; P < .001; and 87.6% in dcSSc; P < .001). By contrast, the prevalence of interstitial lung disease was similar in ssSSc and lcSSc (49.8% and 57.1%; P = .03) but significantly higher in dcSSc (75.0%; P < .001). Skin telangiectasias were associated with diastolic dysfunction in patients with ssSSc (odds ratio, 4.778; 95% CI, 2.060-11.081; P < .001). The only independent factor for the onset of skin fibrosis in ssSSc was the positivity for anti-Scl-70 antibodies (odds ratio, 3.078; 95% CI, 1.227-7.725; P = .02). Survival rate was higher in patients with ssSSc (92.4%) compared with lcSSc (69.4%; P = .06) and dcSSc (55.5%; P < .001) after up to 15 years of follow-up. Conclusions and Relevance: Systemic sclerosis sine scleroderma should not be neglected considering the high prevalence of interstitial lung disease (>40%) and SSc renal crisis (almost 3%). Patients with ssSSc had a higher survival than other subsets. Dermatologists should be aware that cutaneous findings in this subgroup may be associated with internal organ dysfunction. In particular, skin telangiectasias in ssSSc were associated with diastolic heart dysfunction.

Use of platelet inhibitors for digital ulcers related to systemic sclerosis: EUSTAR study on derivation and validation of the DU-VASC model.

OBJECTIVE: To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. METHODS: We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. RESULTS: Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. CONCLUSION: The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Delphi-Based Consensus on Interstitial Lung Disease Screening in Patients with Connective Tissue Diseases (Croatian National-Based Study).

The aim of this study was to develop a Croatian Delphi-based expert consensus for screening interstitial lung disease (ILD) associated with connective tissue disease (CTD). A systematic literature review was conducted on risk factors for the development of ILD, prevalence and incidence of ILD, diagnostic and screening methods for ILD, and prognosis of ILD in idiopathic inflammatory myopathy (IIM), mixed connective tissue disease (MCTD), primary Sjögren's syndrome (pSS), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc) were performed. Based on the evidence found, experts developed questionnaires for screening and monitoring ILD in each CTD, which were provided via an online survey. Following the electronic survey, two screening algorithms were developed based on the consensus opinions. The detection strategy for ILD included high-resolution computed tomography (HRCT) in addition to pulmonary function testing for IIM, MCTD, and SSc. and pulmonary function testing for newly diagnosed pSS, RA and SLE. However, in patients with identified risk factors for ILD HRCT, these tests should also be performed. A screening strategy for early identification of patients with various CTD-ILD was first developed by a multidisciplinary team of rheumatologists, pulmonologists, and radiologists to identify early CTD patients at risk of ILD, a severe extra-articular manifestation of CTD.

Clinical efficacy and safety of adalimumab versus etanercept in patients with ankylosing spondylitis and total spinal ankylosis in Croatia: a multicentre 12-month follow-up study.

OBJECTIVE: To evaluate the 12-month efficacy and safety profile of adalimumab and etanercept in patients with ankylosing spondylitis (AS) and total spinal ankylosis (TSA). TYPE OF STUDY DESIGN: Case-series follow-up study. DESIGN: Twenty-eight patients (26 men and 2 women) with active AS (BASDAI > 4) and TSA were treated as follows: 19 patients receiving adalimumab and 9 patients receiving etanercept. Twelve-month data related to the efficacy and safety of these two TNF-alpha inhibitors were evaluated. The primary endpoint was ASAS 20 (the ASsessment in AS International Working Group criteria for 20% improvement) at weeks 12 and 52. Other measures that were evaluated were function (BASFI), disease activity (BASDAI), patient's and physician's global disease assessment on visual analogue scale (VAS) and C-reactive protein. RESULTS: In both adalimumab and etanercept groups, there was a significant improvement in all observed variables (baseline compared to weeks 12 and 52). This improvement was sustained for the whole follow-up period. In the adalimumab group, at week 12, ASAS 20 was achieved in 18/19 patients and at week 52 in 17/19 patients. In the etanercept group, at week 12 ASAS 20 was achieved in all patients and at week 52 in 6/9 patients. CONCLUSION: In patients with active AS and TSA, adalimumab and etanercept treatment showed significant improvement in function and disease activity. No serious side effects or adverse effects were observed in our cohort. Key Points • TNF-alpha inhibitors can be effective treatment options for patients with AS and having total spinal ankylosis. • Patients with advanced AS should not be disregarded as good candidates for treatment with biologic disease-modifying antirheumatic drugs.

2019 ACR/EULAR classification criteria and therapy in predicting organ damage accrual in patients with childhood-onset systemic lupus erythematosus: A retrospective study over the last 29 years.

OBJECTIVE: We explored damage occurrence in patients with childhood-onset SLE (cSLE) and aimed to predict the risk of organ damage occurrence in time. METHODS: The retrospective study included patients treated for cSLE at the Centre of Reference for Pediatric and Adolescent Rheumatology of the Republic Croatia over a 29-year period. RESULTS: The disease development of 97 patients (77 females) with cSLE was examined. The median (Q1, Q3) follow-up time was 6.5 (2.3, 12.0) years. SDI was determined at 5 time points (6, 12, 24, 36 months, and last follow-up). Thirty-eight patients (48%) had organ damage at the last follow-up. Prepubertal group of patients showed higher SLEDAI scores at the disease onset, while post-pubertal group had significantly lower proportion of patients with relapses. We estimated the time from the first symptom to the moment of damage and our findings suggest that it is unlikely that organ damage will occur in 50% of patients in the first 6 years since the diagnosis. The number of 2019 ACR/EULAR classification criteria at the time of diagnosis associated with SDI determined after 1 year of the follow-up period. The patients who received higher doses of glucocorticoids accumulated damage faster and mycophenolate mofetil was found to be a more frequent therapy in patients with SDI ≥3. CONCLUSION: Knowing that damage will most likely happen after the first 6 years after diagnosis in 50% of patients enables physicians to better predict damage occurrence. High number of 2019 ACR/EULAR criteria and treatment with glucocorticoids in childhood-onset SLE are associated with damage accrual and these findings could enable us to detect patients which should be closely monitored for higher risk of damage development.

Successful IL-17A inhibitor cycling in psoriatic arthritis patient: a case report and a literature review.

Psoriatic arthritis is an inflammatory arthritis with heterogeneous disease presentation. The most affected clinical domain of the disease determines the therapeutic approach. We report the case of a 34-year-old man with all six crucial domains of psoriatic arthritis (psoriasis, peripheral arthritis, axial skeletal manifestations, dactylitis, nail changes, and enthesitis) treated unsuccessfully with conventional synthetic DMARDs, NSAID's, and steroids as well as topical treatment and phototherapy. With golimumab as the first line of bDMARD partial remission was achieved. After 24 months the treatment was switched to secukinumab due to secondary inefficacy. The psoriasis and psoriatic arthritis relapsed after 21 months of treatment with secukinumab. The patient was cycled to ixekizumab with an excellent result. IL-17A inhibitor cycling may be a successful treatment option in some difficult to treat psoriatic arthritis patients.

Dramatically prolonged coagulation screening tests in a patient with positive lupus anticoagulant and monoclonal immunoglobulin M without bleeding manifestations.

BACKGROUND: Concomitant presence of lupus anticoagulant (LA) and monoclonal immunoglobulin in the same patient is uncommon and the influence of this finding on coagulation results is still unknown. CASE REPORT: We present a patient with a diagnosis of systemic lupus erythematosus (SLE) and secondary antiphospholipid syndrome (APS) with permanently positive LA who presented with accidental finding of newly discovered monoclonal IgM in a high concentration and dramatically prolonged prothrombin time (PT) and activated partial thromboplastin time (aPTT), without bleeding manifestations. CONCLUSION: Concomitant presence of extremely prolonged PT and aPTT with unusual coagulation reaction kinetics, consistent LA ratio over the follow-up period and normalization of coagulation screening results with decreasing monoclonal IgM concentration elicited suspicion that PT and aPTT prolongation could be attributed to M-protein with antiphospholipid specificity. Low LA-sensitive aPTT reagent Actin FS demonstrated exceptional sensitivity, whereas human placental thromboplastin in contrast to recombinant reagents showed significantly lower sensitivity to monoclonal IgM with antiphospholipid specificity. Changes in the activity of SLE observed during the follow-up period were inversely related to monoclonal IgM concentration, while the presence of secondary APS was consistent. Described analytical interference on PT and aPTT without bleeding manifestation should point towards suspicion of previously unidentified monoclonal IgM with antiphospholipid sensitivity.

Properties of Uncommon Indirect Immunofluorescence Staining Patterns Determined during Antinuclear Antibody Detection on HEp-2 Cells.

In this study, we aimed to assess the prevalence of uncommon staining patterns found during testing for the presence of antinuclear antibodies (ANA) and to determine their association with certain antibodies and clinical diagnoses. Presence of ANA and the staining pattern was determined in 10955 samples using indirect immunofluorescence (IIF) on HEp-2 cells. ANA-positive samples were assessed for presence of 14 specific antibody types using a microbead based system. Demographic data (age, sex) and clinical diagnoses were collected from the referral documentation. Particular staining patterns were then compared with a representative comparison group comprised of samples with common staining patterns using these criteria. There were 22 patterns present in less than 3% of samples each and these were jointly present in 42.43% of ANA-positive samples. Specific antibodies were found in proportions similar to the comparison group (46.06%) and varied significantly between patterns. Likewise, there were significant differences in antibody distribution in particular patterns. Some patterns were associated with presence of rheumatic diseases or inflammatory arthropathies, while in others there was a concurrent diagnosis of liver disease, or a neoplastic process. Many of the uncommon IIF patterns have distinctive characteristics that warrant further investigation in order to determine their role in diagnosing various diseases, not limited only to the illnesses of the rheumatic spectrum. IIF on HEp-2 cells remains an irreplaceable method because of the diversity of ANA, only a number of which can be detected using other standardised methods.

Demyelinating disease (multiple sclerosis) in a patient with psoriatic arthritis treated with adalimumab: a case-based review.

Over the past two decades, tumor necrosis factor-α (TNF-α) inhibitors became one of the most important drugs in the treatment of patients with psoriatic arthritis. Unfortunately, some of the patients exhibit unwanted side effects of the treatment. We describe a patient with psoriasis, psoriatic arthritis and uveitis who was treated with adalimumab and after 4 months of the treatment developed clinical and neuroradiological signs of demyelinating disease of the central nervous system. She experienced no signs and symptoms of neurological disease prior to adalimumab administration. After a detailed neurological work-up she was diagnosed with relapsing-remitting type of multiple sclerosis and treated with oral and pulse glucocorticoids and later with dimethyl fumarate. Adalimumab was discontinued. The question remains was the demyelination induced by the TNF-α blockade or was it unmasked by the introduction of the cytokine blocking agent. In patients suffering from inflammatory arthritis, treating disease to target as well as a close follow-up and knowledge of potential side effects of treatment remains crucial in good clinical practice.

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria item performance.

BACKGROUND/OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 classification criteria for systemic lupus erythematosus system showed high specificity, while attaining also high sensitivity. We hereby analysed the performance of the individual criteria items and their contribution to the overall performance of the criteria. METHODS: We combined the EULAR/ACR derivation and validation cohorts for a total of 1197 systemic lupus erythematosus (SLE) and n=1074 non-SLE patients with a variety of conditions mimicking SLE, such as other autoimmune diseases, and calculated the sensitivity and specificity for antinuclear antibodies (ANA) and the 23 specific criteria items. We also tested performance omitting the EULAR/ACR criteria attribution rule, which defines that items are only counted if not more likely explained by a cause other than SLE. RESULTS: Positive ANA, the new entry criterion, was 99.5% sensitive, but only 19.4% specific, against a non-SLE population that included other inflammatory rheumatic, infectious, malignant and metabolic diseases. The specific criteria items were highly variable in sensitivity (from 0.42% for delirium and 1.84% for psychosis to 75.6% for antibodies to double-stranded DNA), but their specificity was uniformly high, with low C3 or C4 (83.0%) and leucopenia <4.000/mm³ (83.8%) at the lowest end. Unexplained fever was 95.3% specific in this cohort. Applying the attribution rule improved specificity, particularly for joint involvement. CONCLUSIONS: Changing the position of the highly sensitive, non-specific ANA to an entry criterion and the attribution rule resulted in a specificity of >80% for all items, explaining the higher overall specificity of the criteria set.

Upadacitinib versus placebo or adalimumab with background methotrexate in patients with rheumatoid arthritis and an inadequate response to methotrexate: a subgroup analysis of a phase III randomized controlled trial in Central and Eastern European patients.

BACKGROUND: In the randomized, phase III, global SELECT-COMPARE study, upadacitinib 15 mg demonstrated efficacy at week 12 versus placebo and adalimumab with methotrexate (MTX) in patients with rheumatoid arthritis and inadequate response to MTX, which was maintained over 48 weeks. This post hoc analysis of SELECT-COMPARE reports the efficacy and safety of upadacitinib in Central and Eastern European (CEE) patients. METHODS: Patients were randomized 2:2:1 to upadacitinib 15 mg once daily, placebo, or adalimumab 40 mg every other week, and continued MTX. Efficacy and safety were assessed through 48 weeks. Primary endpoints were the achievement of ≥20% improvement in American College of Rheumatology response criteria and Disease Activity Score in 28 joints with C-reactive protein <2.6 responses at week 12 for upadacitinib versus placebo. No statistical comparisons were conducted. RESULTS: A total of 596 patients from 12 CEE countries were randomized. At week 12, a numerically greater proportion of patients receiving upadacitinib versus placebo or adalimumab achieved ≥20% improvement in American College of Rheumatology response criteria (72% versus 33% and 59%), Disease Activity Score in 28 joints with C-reactive protein <2.6 (26% versus 4% and 11%), low disease activity and remission, and improved physical function, with results maintained over 48 weeks. Upadacitinib treatment numerically inhibited structural progression versus placebo at week 26. Serious infection and herpes zoster rates were numerically higher with upadacitinib versus adalimumab (2.7 versus 1.7 and 2.3 versus 1.1 events/100 patient-years, respectively) over 48 weeks. CONCLUSION: Consistent with the global population of patients with rheumatoid arthritis and an inadequate response to MTX, in CEE patients, upadacitinib 15 mg demonstrated clinical and functional improvements versus placebo and adalimumab, radiographic improvements versus placebo, and reasonable safety, over 48 weeks.

Corrigendum to "The Association of TNF-Alpha Inhibitors and Development of IgA Nephropathy in Patients with Rheumatoid Arthritis and Diabetes".

[This corrects the article DOI: 10.1155/2020/9480860.].

Misleading symptoms of hereditary angioedema type II mimicking familial mediterranean fever.

Hereditary angioedema (HAE) is a rare, debilitating and potentially life-threatening disease characterized by recurrent attacks of oedema. With the development of new therapies and better availability of diagnostic tools, important advances have been made. However, the disease still remains frequently misdiagnosed and inadequately treated. Familial Mediterranean fever (FMF) is an autoinflammatory syndrome comprised of serositis, fever, arthritis and skin involvement. Both diseases can cause severe abdominal pain resembling that of acute abdomen. We report a case of three family members that presented with various symptoms that could fit in a clinical picture of both diseases, only to confirm a diagnosis of HAE type II after a diagnostic delay of many years.

Performance of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in early disease, across sexes and ethnicities.

OBJECTIVES: The European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) 2019 Classification Criteria for systemic lupus erythematosus (SLE) have been validated with high sensitivity and specificity. We evaluated the performance of the new criteria with regard to disease duration, sex and race/ethnicity, and compared its performance against the Systemic Lupus International Collaborating Clinics (SLICC) 2012 and ACR 1982/1997 criteria. METHODS: Twenty-one SLE centres from 16 countries submitted SLE cases and mimicking controls to form the validation cohort. The sensitivity and specificity of the EULAR/ACR 2019, SLICC 2012 and ACR 1982/1997 criteria were evaluated. RESULTS: The cohort consisted of female (n=1098), male (n=172), Asian (n=118), black (n=68), Hispanic (n=124) and white (n=941) patients; with an SLE duration of 1 to <3 years (n=196) and ≥5 years (n=879). Among patients with 1 to <3 years disease duration, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 81%). The EULAR/ACR criteria performed well in men (sensitivity 93%, specificity 96%) and women (sensitivity 97%, specificity 94%). Among women, the EULAR/ACR criteria had better sensitivity than the ACR criteria (97% vs 83%) and better specificity than the SLICC criteria (94% vs 82%). Among white patients, the EULAR/ACR criteria had better sensitivity than the ACR criteria (95% vs 83%) and better specificity than the SLICC criteria (94% vs 83%). The EULAR/ACR criteria performed well among black patients (sensitivity of 98%, specificity 100%), and had better sensitivity than the ACR criteria among Hispanic patients (100% vs 86%) and Asian patients (97% vs 77%). CONCLUSIONS: The EULAR/ACR 2019 criteria perform well among patients with early disease, men, women, white, black, Hispanic and Asian patients. These criteria have superior sensitivity than the ACR criteria and/or superior specificity than the SLICC criteria across many subgroups.